This project is to develop and support three state-of-the-art optical instruments that provide microscopic access to the living retina, and use them to obtain a clearer understanding of how the human visual system works. They will be used to answer questions about the most important and the most challenging region in the retina to study, the fovea. The instruments are built upon two key technical strengths - adaptive optics scanning laser ophthalmoscope (AOSLO) systems and accurate, high-speed eye-motion tracking. Adaptive optics (AO) technology corrects the imperfections in the eye and can be used to generate microscopic views of the living retina. AO also enables the delivery of ultra-sharp images to the retina. Eye tracking is used to measure and compensate for ever-present eye motion. Together, these allow for accurate visualization, tracking and delivery of light to retinal features as small as single cone photoreceptors, enabling measurements of properties of spatial and color vision on an unprecedented scale. Although the three systems will be identical and will be used to test vision on a cellular scale, the scope of study for each system will be very different. The AOSLO at the University of Alabama, Birmingham will be used to test vision in primates, the AOSLO at the University of California, Berkeley will be used to perform advanced vision testing on healthy human eyes, and the AOSLO at the University of California, San Francisco will be used to study patients with eye disease. The key advantage of having the BRP manage three identical systems is that it will facilitate hardware innovations plus rapid translation of knowledge and innovative testing from animal models to the clinic. Briefly, the specific aims are: Aim 1: Develop and deploy state-of-the-art AOSLO systems at each site. Demonstrate performance by performing objective densitometry measures in monkeys and humans to map the three classes of cone photoreceptor that subserve color vision. Aim 2: Develop improved eye tracking and stimulus delivery capabilities in each system. Confirm performance by using subjective psychophysical tests to map the same three classes of cone photoreceptor as in Aim 1. Aim 3: Perform a series of experiments in monkeys and humans to map the connections and interactions within and between the retina and the brain and to study how we see the world as stable even though our eyes are in constant motion. Aim 4: Apply advanced vision testing methods in the clinic to discover mechanisms for cone death in different diseases, to monitor changes in cone function and structure during disease progression and to test the efficacy of treatments that aim to stop or slow disease progression. Aim 5: Make eye tracking and targeted stimulus delivery capabilities accessible to a wider audience by providing software, hardware designs and a forum for anyone interesting in building similar advanced systems.